NMR (nuclear magnetic resonance) and MRI (magnetic resonance imaging) are useful systems that have been developed and provide information for chemically specific kinetics and imaging, but are typically limited by poor signal-to-noise. Recently, methods have been developed for generating liquid samples of molecules with spin polarization of order 10−1, known as hyperpolarization, at sites with spin-lattice relaxation times of tens of seconds, and enhancement of 104-105 over ambient temperature experiments on samples initially at equilibrium in typical high magnetic fields[1-5].
In addition to the degree of spin ordering, another important property is the lifetime over which the order persists when out of equilibrium. For N spins ½ there are at least 2N-1 quasiconstants under the effective spin Hamiltonian. Of particular value are those types of spin order with the longest lifetimes, allowing observations over longer periods of time. These include the longitudinal spin polarization, proportional to the expectation value of the z component Izi of the angular momentum of the ith spin, whose lifetime against equilibration is the spin-lattice relaxation time T1i. In certain cases the relative ordering of spins, such as the two-spin scalar order Ii·Ij can be created and can have an even longer lifetime TS. As a resource for hyperpolarized NMR, scalar order was introduced as symmetrization order in techniques known as PASADENA [6-7] and ALTADENA [8], in which molecular addition of parahydrogen prepares a molecule with a pair of protons in the singlet spin state, which is convertible to observable polarization either on these two protons or on other spins coupled to them within a molecule or transient complex.
Transfer of scalar order was demonstrated to polarize 13C[9] using a pulse sequence derived from INEPT[10]. Additional methods for this transfer from scalar order to polarization on a resolved third spin are known[6, 11-15]. In this context, transfer of order to the heteronucleus followed by its observation as polarization may increase the time during which hyperpolarization is available, allow better chemical discrimination, and increase the contrast against the background signals from other weakly polarized molecules.
After reaction of a precursor molecule with parahydrogen, the singlet state is typically no longer an eigenstate of the new system, due to the location of the nascent protons in magnetically inequivalent sites. The subsequent oscillatory spin evolution upon molecular addition is typically averaged over the distribution of times at which molecular addition occurs, thereby irreversibly reducing the spin order. The scalar order may be preserved by application of decoupling to the hydrogen, such as a train of π pulses[2, 13-14, 16]. The role of such scalar locking sequences in mitigating other relaxation mechanisms has been elucidated and applications made in which the scalar order is initially created by conversion from equilibrium or nonequilibrium polarization[17-19] rather than by molecular addition of a molecule with scalar order.
Hyperpolarized signals are typically generated on sites that are insensitive spin ½ heteronuclei such as 13C or 15N, which are preferred for their longer relaxation times and often superior chemical specificity in comparison to 1H (e.g., protons on the order of 1 second and carbon and nitrogen on the order of 1 minute). Longer relaxation time allows time to transfer the highly polarized molecules from the polarizer to the system of interest and to allow time for chemical dynamics with minimum polarization loss. Nuclei with lower gyromagnetic ratios tend to have longer spin-lattice relaxation times, so the most desirable targets from the point of view of long spin lifetimes are also the least desirable from the point of view of sensitivity. The gyromagnetic ratio enters linearly in both the magnitude of the detected magnetic moment and through the proportionality of inductive signals to Larmor frequency, offsetting the gains from hyperpolarization in comparison to detection on more sensitive nuclei.
Transferring the polarization[10, 20-21] from less sensitive to more sensitive spins in combination with hyperpolarization has been proposed to recover this lost sensitivity[22-25] and, for the purposes of MRI, additionally allows obtaining a given spatial resolution with practical pulsed field gradient power. When N equivalent protons I couple to the heteronucleus S, this transfer is efficiently produced by the refocused INEPT (insensitive nucleus enhanced by polarization transfer) sequence[10, 20-21] in the “reverse” direction. This strategy has previously been extended to hyperpolarized samples[22-23, 25] in which the pulse sequence was designed to optimally polarize the target protons at the expense of fully depleting the heteronuclear hyperpolarization in the interrogated ensemble of molecules. In the special case of a system with uniform chemical composition (e.g. a solution in a NMR tube), a longer time course may be generated by spatially selecting different voxels for probing a reaction with complete S to I transfer at different times.[25]
Despite the progress made in NMR and MRI techniques, there is a need in the art for improved methods and systems to maximize the information content obtained during the application of NMR and MRI techniques.